Dialogue and Diagnosis - American Osteopathic Association

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occur, she was instructed to stop taking the drug and contact us immediately. In a small percentage of patients taking GLP-1 receptor agonists, abdominal pain has been associated with acute pancreatitis. As her physician, I selected liraglitide for Gloria, because its use does not involve dose adjustments for patients with renal insuffici ency, 30 and it can be injected once daily without regard to caloric intake. However, I will want to closely monitor her serum creatinine since its 1.2 mg/dL as changing renal function is a real issue to consider in patients with long-term diabetes. I started Gloria on liraglitide 0.6 mg daily and titrated the dosage to 1.2 mg daily during the next 7 to 10 days. As liraglitide was initiated, I instructed Gloria to suspend her use of glimepiride and to reduce her dose of insulin glargine by 10%, in order to reduce her risk of hypo - glycemia. 27 With this treatment regimen, Gloria did not experience nausea, vomiting, or hypoglycemia, and she was pleased that her FPG levels began to decrease within days of starting liraglitide. Within 12 weeks of liraglitide initiation, Gloria’s HbA 1c level was at the American Diabetes Association target of 6.9%, and her weight had not increased. Future of insulin supplementation Although currently available insulin analogs do not represent exact physiologic replacements for endogenous basal bolus insulin, the continued evolution of insulin products and delivery devices is substantially improving the ease of insulin use for patients with T2DM. The refinement in insulin supplementation that has occurred in the last 20 years is dramatic and ongoing. The future holds additional possibilities for improving glycemic control with less hypoglycemia, less variability, and potentially less weight gain and greater patient convenience. Currently under review by the Food and Drug Administration is insulin degludec, a very long-acting insulin which is in Phase III clinical trials. Insulin degludec forms soluble multi-hexamers upon subcutaneous injection, resulting in a depot from which insulin is continuously and slowly absorbed into circulation to provide an ultralong and steady action profile. 31 This longacting insulin is administered once daily, but because of its long halflife, it can be considered to be a very “forgiving” insulin—meaning that if a patient forgets to take insulin at the same time each day, some variability in the dosing will not affect blood glucose levels. Compared with insulin glargine, insulin degludec has much less pharmacodynamics variability and, thus, a more predictable glucose-lowering effect from day to day. 32 In studies of patients with either T1DM or T2DM, insulin degludec was associated with less nocturnal hypo - glycemia compared to insulin glargine. 33,34 Insulin degludec is also being studied as part of combination therapy with insulin aspart (as essentially a bolus boost of rapidacting insulin). When given once daily in the evening, this combination improved glucose control throughout the day (as measured by 30 Dialogue and Diagnosis // September 2012
8-point glucose levels) and did so signifi cantly better than insulin glargine for postdinner hyper - glycemia. 35 Another novel insulin, a PEGylated formulation of insulin lispro is in development but is not far along and has less information available. This PEGylated insulin (LY2605541), which has entered the Phase-II stage of clinical develop - ment, has a long duration of action. Compared to insulin glargine, LY2605541 was associated with improved glycemic control and some weight loss in patients with T1DM (ie, those with a mean baseline weight of 183 lb [83 kg]. The baseline weight is only important if we know how much weight loss patients achieved. 36 Studies with this agent are currently recruiting participants with T2DM. (Information on this recruitment can be found at http://clinicaltrials.gov/.) There are also advances in prandial (mealtime) insulin develop - ment. A novel ultrarapid-acting insulin in development is associated with less variability among patients than regular human insulin. 37 There also is an investigational ultrarapidacting inhaled insulin that achieves maximum blood concentrations within 15 minutes and has a very short duration of action (~2-3 hours). 38 Insulin delivery by inhaler may be possible in the future. Techno - sphere technology is being investigated as a way to make pulmonary delivery of proteins and peptides possible, essentially by using a dry powder with nanometer-sized particles to carry active drugs so that the drugs rapidly dissolve upon lung contact. In the use of this techno - logy for prandial insulin delivery, less weight gain and fewer hypo - glycemic events were observed in combination with a basal insulin, compared to injectable prandial insulin analog added to basal insulin. 39 The safety and tolerability profile was similar for both treat - ment regimens, apart from increased occurrence of cough and changes in pulmonary function in the group receiving inhaled insulin plus insulin glargine. 39 Final notes Advances in pharmaceutical development have greatly increased the therapeutic options available for manage ment of T2DM and the possibilities for combination therapy strategies. Technological develop ments also are increasing the number of available injectable therapies. Patients should be made aware of these therapies as viable options in their care. Patient education and involvement can improve treatment adherence and reduce the rates of poor outcomes associated with the epidemic of diabetes mellitus. References 1. Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58(4):773-795. 2. Wright A, Burden AC, Paisey RB, Cull CA, Holman RR; UK Prospective Diabetes Study Group. Sulfonylurea inadequacy: efficacy of addition of insulin over 6 years in patients with type 2 diabetes in the UK Prospective Diabetes Study (UKPDS 57). Diabetes Care. 2002;25(2):330-336. 3. Bailey CJ, Kodack M. Patient adherence to medication requirements for therapy of type 2 diabetes. Int J Clin Pract. 2011;65(3):314-322. doi: 10.1111/j.1742-1241.2010.02544.x. 4. Pratley RE, Gilbert M. Clinical management of elderly patients with type 2 diabetes mellitus [review]. Postgrad Med. 2012;124(1):133-143. 5. Ritz E. Limitations and future treatment options in type 2 diabetes with renal impairment. Diabetes Care. 2011;34 suppl 2:S330-S334. 6. Fonseca VA. Incretin-based therapies in complex patients: practical implications and opportunities for maximizing clinical outcomes: a discussion with Dr Vivian A. Fonseca. Am J Med. 2011;124(1 suppl):S54-S61. 7. Akram K, Pedersen-Bjergaard U, Borch- Johnsen K, Thorsteinsson B. Frequency and risk factors of severe hypoglycemia in insulin-treated type 2 diabetes: a literature survey. J Diabetes Complications. 2006;20(6):402-408. 8. Nakar S, Yitzhaki G, Rosenberg R, Vinker S. Transition to insulin in Type 2 diabetes: family physicians’ misconception of patients’ fears contributes to existing barriers. J Diabetes Complications. 2007;21(4):220-226. (continued) Dialogue and Diagnosis // September 2012 31
Page 1 and 2: Volume 2 Number 2 September 2012 In
Page 3 and 4: Introducing and adjusting injectabl
Page 5 and 6: the fact that he was obviously upse
Page 7 and 8: insulin therapy include a sense of
Page 9 and 10: Basal insulin alone Sequential addi
Page 11 and 12: speaking Hispanic patients reported
Page 13 and 14: AFTER METFORMIN Introducing and tit
Page 15 and 16: Figure 1. The simultaneously increa
Page 17 and 18: Figure 3. Key benefits and risks of
Page 19 and 20: Compounds Exenatide (approved 2005
Page 21 and 22: PATIENT DIALOGUE Are GLP-1 receptor
Page 23 and 24: missed and the next scheduled dose
Page 25 and 26: Adding glucagon-like peptide-1 rece
Page 27 and 28: hips, which, with her excess weight
Page 29 and 30: T2DM is achieving glycemic control
Page 31: Patient instruction Clearly discuss
Page 35 and 36: InsideOut (continued from inside fr

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